Renal insufficiency originating from functional disorders of kindney is a disease directly related to life because it brings abnormal increases of blood serum urea nitrogen (BUN), blood creatinine, blood methylguanidine and the like and causes various affections. Various artificial kidneys are currently used as conservative treatment for renal insufficiency, and major kinds of these artificial kidneys can remove body wastes such as urea from blood of patients by performing hemodialysis or blood filtration for the patients with using a module comprising a hollow fiber membrane.
Materials for such a hollow fiber membrane used are polymers such as cellulose, cellulose acetate, polyamide, polyacrylonitrile, ethylene-vinylalcohol copolymer, poly(methyl methacrylate) and polysulfone. Among these, hollow fiber membranes comprising a polysulfone resin are superior in heat resistance, chemical resistance, mechanical strength, biological compatibility and the like, and they have attracted attention recently.
With recent progress of artificial dialysis treatment technologies, patients taking artificial dialysis for more than 10 years have increased in number, and much expression of complications such as anemia, bone/joint abnormality and neuropathy has been found in these patients.
Causal substances of these symptoms attracting attention are low-molecular-weight proteins having molecular weight of 10,000 to 30,000 or medium-molecular-weight substances having molecular weight of several thousands to tens of thousands, which are contained in blood. An example of a low molecular weight protein is .beta.2-microglobulin (molecular weight of 11,800) which is a causal substance of a carpal syndrome. Thus, a hollow fiber membrane for artificial dialysis has been required to have such selective separability that low-molecular-weight proteins having molecular weight of 10,000 to 30,000 easily permeate but a useful protein, albumin (molecular weight of 69,000) does not permeate, as well as removal performance for low-molecular-weight substances such as urea and creatinine.
As a hollow fiber membrane for blood purification comprising a polysulfone resin, a hollow fiber membrane containing a hydrophilic polymer such as poly(vinyl pyrrolidone) and poly(ethylene glycol) is disclosed in Japanese Kokoku Publication J5-54373 and Japanese Kokai Publication J6-296686. It is obtained by preparing a membrane after mixing a hydrophilic polymer with a polysulfone resin in a form of spinning solution not forming a membrane.
Additionally, Japanese Kokai Publication J6-238139 discloses a technology for obtaining such a polysulfone hollow fiber membrane for blood purification containing a hydrophilic polymer by preparing a polysulfone hollow fiber membrane for blood purification, assembling them into a module, and then introducing a hydrophilic polymer solution into the inside of the said hollow fiber to coat the inner side of the hollow fiber membrane with the said hydrophilic polymer.
However, these hollow fiber membranes for blood purification have some problems in safety because there is a possibility that a hydrophilic polymer may be dissolving out in clinical applications. In addition, membrane performance may change with time by dissolution of a hydrophilic polymer into a module-filling liquid after assembling a module. Thus technologies disclosed in Japanese Kokai Publication J6-238139 and Japanese Kokai Publication J6-339620 have tried to prevent this dissolution by crosslinking poly(vinyl pyrrolidone) with the radiation treatment or heat-treatment, but the results are not satisfactory.
Moreover, these membranes have such drawbacks that mechanical strength of a membrane itself in the hollow fiber membrane for blood purification may be lowered and that water permeability may also decrease when content of a hydrophilic polymer in the hollow fiber membrane for blood purification increases. Furthermore, there are also such a drawback that special equipment for storage is necessary because these membranes absorb moisture in air during storage after preparing them.
In Japanese Kokai Publication J61-232860 and Japanese Kokai Publication J63-105770, a polysulfone hollow fiber membrane not containing a hydrophilic polymer is disclosed, but it can be used only as a plasma separating membrane to filtrate and separate plasma from blood, or a plasma fractionating membrane to separate and recover a specific plasma component selectively from the separated plasma. Thus it is not able to be used as a hollow fiber membrane for blood purification.
Japanese Kokai Publication J61-113460 discloses a membrane for continuous arterio-venous hemofiltration for hemodialysis or continuous blood filtration intended for treatment of acute renal insufficiency, but it is not practical for hemodialysis or blood filtration intended for treatment of chronic renal insufficiency.
In addition, no literature discloses a polysulfone membrane for blood purification not containing a hydrophilic polymer, which can remove selectively and efficiently low-molecular-weight proteins having molecular weight of 10,000 to 30,000 contained in blood.